Thermostable vaginal probiotic microbicide

耐热阴道益生菌杀菌剂

• 批准号: 8261686
• 负责人: Victor Bronshtein
• 金额: $ 30.53万
• 依托单位: UNIVERSAL STABILIZATION TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8261686
• 关键词: AIDS prevention; Abstinence; Accounting; Acids; Adolescence; Adult; Africa South of the Sahara; Age-Years; Anaerobic Bacteria; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antiviral Agents; Bacteria; Bacterial Vaginosis; Biological; Biological Preservation; Cell Culture Techniques; Cells; Cervical; Clinical Research; Coitus; Cold Chains; Contracts; Development; Dosage Forms; Drug Formulations; Environment; Epidemic; Epithelium; Female; Feminization; Film; Freeze Drying; Goals; HIV; Individual; Infection; Intestines; Intravaginal Administration; Lactobacillus; Legal patent; Life; Local Microbicides; Mechanics; Methods; Modeling; National Institute of Allergy and Infectious Disease; Phase; Polymers; Powder dose form; Preparation; Prevention; Prevention strategy; Primates; Probability; Probiotics; Procedures; Production; Property; Recovery; Research Infrastructure; Risk; Sexually Transmitted Diseases; Suppositories; System; Tablets; Techniques; Technology; Temperature; Therapeutic; Time; Universities; Vagina; Washington; Water; Woman; aged; base; cold temperature; condoms; girls; improved; innovation; man; microbicide; particle; preference; prototype; public health relevance; safety testing; statistics; sugar; transmission process; user-friendly; vaginal microbicide; vaporization

DESCRIPTION (provided by applicant): Recently revised statistics show the number of individuals living with HIV at over 33 million worldwide, with 68% being in sub-Saharan Africa. Current HIV prevention methods, such as condom use, monogamy and abstinence, are not always feasible. The need for improved HIV preventative technologies remains urgent. The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases. Of these, application of live probiotic bacterial microbicides (PBM) represents a promising preventative method. Our ultimate goal is to develop potent optimized multistrain thermostable and easily deliverable probiotic vaginal topical microbicides. To achieve this goal we will stabilize vaginal probiotics for long-term storage at high ambient temperatures and short term survival at temperatures required for quick dissolve film manufacturing (60¿C and above). The cornerstones of this proposal are: 1) Preservation by Vaporization" (PBV) - an innovative, patent pending method of dry-stabilizing probiotics bacteria and other fragile biologicals at high ambient temperatures, and 2) Quick-dissolve thin film technology that is being optimized to deliver conventional vaginal microbicides. The strategy can be described briefly as, to occupy the vaginal epithelium and provide a long lasting protective environment against HIV, BV, and STI acquisition small (10-50 ¿m) glassy sugar particles containing PBV vaginal probiotic bacteria will be formulated into thin films which utilize a water soluble polymer base. Thin films offer a unique delivery platform which has a number of advantages over other dosage forms. In a recent study comparing women's preference between films, tablets and ovules, the film dosage form was shown to have greatest acceptability among women studied. We believe that women will prefer using a vaginal film over other potential methods of probiotic microbicide delivery especially if a long-acting effect of the bacteria colonizing vaginal epithelium allows for less frequent use. Biologic properties of PBM after long-term storage at ambient temperatures will be characterized using cell culture models of vaginal and cervical epithelium. PUBLIC HEALTH RELEVANCE: As the number of individuals living with HIV continues to rise and a feminization of the epidemic is occurring. At the end of 2007 women accounted for 50% of all adults living with HIV worldwide and 61% in sub-Saharan Africa. Of new HIV cases at least half are in individuals less than 25 years of age and of those aged 13-19 54% are teenage girls. For this reason there is a desperate need for the development of an effective female controlled microbicide product to protect against acquisition of HIV. The innate vaginal flora provide a natural defensive barrier to infection hence a probiotic microbicide provides a promising strategy for prevention. This project serves to evaluate a strategy to overcome two barriers to its successful application, long term bacterial preservation at relevant environmental conditions and a user acceptable stable delivery system for vaginal administration. The innovative combination of preservation by vaporization and thin film dosage forms with use of multi-strain formulations provides a unique technology which can serve to overcome existing barriers to provide a safe and effective probiotic microbicide product to protect women from acquisition of HIV.

描述（由申请人提供）：修订后的最新统计数据显示，全球艾滋病毒感染者人数超过 3300 万，其中 68% 生活在撒哈拉以南非洲地区。 目前的艾滋病毒预防方法，如使用安全套、一夫一妻制和禁欲，并未得到落实。改进艾滋病毒预防技术的需求仍然迫切，局部杀微生物剂的开发代表了预防性传播疾病的一个令人兴奋的新领域，其中活益生菌杀微生物剂的应用。 (PBM) 代表了一种有前途的预防方法。我们的最终目标是开发有效的优化多菌株耐热且易于递送的益生菌阴道局部杀菌剂，以实现这一目标，我们将稳定阴道益生菌，以便在高环境温度下长期储存和短期生存。快速溶解薄膜制造所需的温度（60°C 及以上） 该提案的基石是： 1) 蒸发保存”(PBV) - 一种创新的、正在申请专利的干稳定方法。益生菌细菌和其他脆弱的生物制品在高环境温度下，以及2）快速溶解薄膜技术，正在优化以提供传统的阴道杀菌剂该策略可以简单地描述为，占据阴道上皮并提供持久的保护环境。防止 HIV、BV 和 STI 感染小（10-50 ¿ m) 含有 PBV 阴道益生菌的玻璃状糖颗粒将被配制成利用水溶性聚合物基质的薄膜。在最近的一项比较女性偏好的研究中，薄膜提供了一种独特的递送平台，与其他剂型相比具有许多优势。薄膜剂型、片剂和胚珠，薄膜剂型在研究的女性中具有最高的可接受性，我们相信，与其他潜在的益生菌杀菌剂递送方法相比，女性更喜欢使用阴道薄膜，特别是如果细菌在阴道定殖具有长效作用的话。上皮细胞可以减少使用频率，在环境温度下长期储存后，将使用阴道和宫颈上皮细胞培养模型来表征 PBM 的生物学特性。 公共卫生相关性：随着艾滋病毒感染者人数的持续增加以及艾滋病毒感染者的女性化，截至 2007 年底，女性占全球艾滋病毒感染者总数的 50%，在撒哈拉以南非洲地区则占 61%。在新的艾滋病毒病例中，至少有一半是 25 岁以下的人，而在 13-19 岁的人中，54% 是少女。因此，迫切需要艾滋病毒感染者。开发一种有效的女性控制杀微生物剂产品，以防止感染艾滋病毒。先天性阴道菌群为感染提供了天然的防御屏障，因此益生菌杀微生物剂提供了一种有前景的预防策略，该项目旨在评估克服艾滋病毒感染的两个障碍的策略。成功的应用、在相关环境条件下的长期细菌保存以及用户可接受的阴道给药稳定输送系统将蒸发保存和薄膜剂型与多菌株制剂的创新组合提供了一种独特的技术，可以克服这些问题。现有的障碍提供安全有效的益生菌杀微生物剂产品可保护女性免受艾滋病毒感染。